Article
Oncology
Thomas G. Martin, Nina Shah, Joshua Richter, David H. Vesole, Sandy W. Wong, Chiung-Yu Huang, Deepu Madduri, Sundar Jagannath, David S. Siegel, Noa Biran, Jeffrey L. Wolf, Samir Parekh, Hearn J. Cho, Pamela Munster, Shambavi Richard, Samira Ziti-Ljajic, Ajai Chari
Summary: This study evaluated the safety and efficacy of Isa and K combination therapy in patients with RRMM. Despite heavily pretreated patients, 70% responded to the treatment, with a median progression-free survival of 10.1 months.
Article
Pharmacology & Pharmacy
Anne-Gaelle Dosne, Xia Li, Man Melody Luo, Ivo Nnane, Meletios A. Dimopoulos, Evangelos Terpos, Pieter Sonneveld, Tobias Kampfenkel, Robin Carson, Himal Amin, Juan Perez Ruixo, Honghui Zhou, Yu-Nien Sun, Yan Xu
Summary: A PPK model was developed to characterize the pharmacokinetics of daratumumab in patients with RRMM. The analysis revealed a relationship between daratumumab exposure and efficacy and safety. The study supports the use of subcutaneous administration of daratumumab at a dose of 1800 mg in combination with Pd for the treatment of RRMM patients.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2023)
Article
Oncology
Evangelos Terpos, Ioannis Ntanasis-Stathopoulos, Efstathios Kastritis, Evdoxia Hatjiharissi, Eirini Katodritou, Evangelos Eleutherakis-Papaiakovou, Evgenia Verrou, Maria Gavriatopoulou, Alexandros Leonidakis, Kyriaki Manousou, Sosana Delimpasi, Panagiotis Malandrakis, Marie-Christine Kyrtsonis, Maria Papaioannou, Argiris Symeonidis, Meletios-Athanasios Dimopoulos
Summary: The study demonstrates that the anti-CD38 monoclonal antibody daratumumab improves bone turnover in patients with multiple myeloma by inducing bone formation and reducing osteoblast inhibition, highlighting its clinical significance.
Article
Oncology
Saad Z. Usmani, Maria-Victoria Mateos, Vania Hungria, Shinsuke Iida, Nizar J. Bahlis, Hareth Nahi, Hila Magen, Michele Cavo, Cyrille Hulin, Darrell White, Valerio De Stefano, John Fastenau, Mary Slavcev, Christoph Heuck, Xiang Qin, Huiling Pei, Tara Masterson, Kristen Lantz, Katharine S. Gries
Summary: In the COLUMBA study, patients receiving daratumumab subcutaneously had higher satisfaction with their cancer therapy compared to those receiving it intravenously. Around 40% of patients experienced changes in satisfaction domain scores exceeding the minimally important difference.
JOURNAL OF CANCER RESEARCH AND CLINICAL ONCOLOGY
(2021)
Article
Oncology
Uros Markovic, Alessandra Romano, Vittorio Del Fabro, Claudia Bellofiore, Anna Bulla, Marina Silvia Parisi, Salvatore Leotta, Massimo Gentile, Clotilde Cangialosi, Iolanda Vincelli, Giuseppe Mineo, Marco Rossi, Massimo Poidomani, Giuseppina Uccello, Cinzia Maugeri, Donato Mannina, Vanessa Innao, Francesco Di Raimondo, Concetta Conticello
Summary: The study shows that daratumumab as a single agent is a safe and well-tolerated regimen in real-life, associated with prolonged progression free survival and overall survival in responding patients. No new safety signals were identified.
FRONTIERS IN ONCOLOGY
(2021)
Article
Oncology
Cyrille Touzeau, Chloe Antier, Philippe Moreau
Summary: The triplet drug combination of daratumumab-carfilzomib-dexamethasone has shown strong clinical efficacy in patients with relapsed multiple myeloma, especially in those who are lenalidomide refractory.
Article
Oncology
Ja Min Byun, Chang-Ki Min, Kihyun Kim, Soo-Mee Bang, Je-Jung Lee, Jin Seok Kim, Sung-Soo Yoon, Youngil Koh
Summary: Extramedullary multiple myeloma (EMD) is a subentity of multiple myeloma (MM) with poor prognosis. This study evaluated the efficacy and safety of daratumumab in combination with multiple drugs for the treatment of EMD. The results showed that the complete remission rate was 35.5% and overall response rate was 67.7%. Long-term responders had a significantly improved progression-free survival. The most common adverse events were hematologic and non-hematologic toxicities.
JOURNAL OF HEMATOLOGY & ONCOLOGY
(2022)
Article
Hematology
Sung-Soo Park, Ja Min Byun, Sung-Soo Yoon, Kihyun Kim, Sung-Hoon Jung, Je-Jung Lee, Chang-Ki Min
Summary: Real-world outcomes of daratumumab monotherapy for relapsed/refractory multiple myeloma showed favorable responses, but certain factors related to trial-unfitness may offset its efficacy. Patients in the modified trial-unfit group had poorer survival outcomes, indicating the potential impact of specific characteristics on treatment efficacy.
BRITISH JOURNAL OF HAEMATOLOGY
(2021)
Review
Oncology
Massimo Offidani, Laura Corvatta, Sonia More, Davide Nappi, Giovanni Martinelli, Attilio Olivieri, Claudio Cerchione
Summary: Immunotherapy with daratumumab has been approved for the treatment of multiple myeloma and has shown significant efficacy in both relapsed-refractory and newly diagnosed patients, utilizing various mechanisms of action to target CD38. Ongoing trials are exploring new combinations with daratumumab to provide further insights into its potential benefits for MM patients.
FRONTIERS IN ONCOLOGY
(2021)
Letter
Medicine, General & Internal
Elif Hindie
Summary: The study found that treatment with teclistamab resulted in a high overall response rate of 63.0% and a median progression-free survival of 11.3 months in patients with relapsed or refractory myeloma. Additionally, the change in serum levels of soluble BCMA correlated with treatment response.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Medicine, General & Internal
Philippe Moreau, Alfred L. Garfall, Niels W. C. J. van de Donk, Hareth Nahi, Jesus F. San-Miguel, Albert Oriol, Ajay K. Nooka, Thomas Martin, Laura Rosinol, Ajai Chari, Lionel Karlin, Lotfi Benboubker, Maria-Victoria Mateos, Nizar Bahlis, Rakesh Popat, Britta Besemer, Joaquin Martinez-Lopez, Surbhi Sidana, Michel Delforge, Lixia Pei, Danielle Trancucci, Raluca Verona, Suzette Girgis, Shun X. W. Lin, Yunsi Olyslager, Mindy Jaffe, Clarissa Uhlar, Tara Stephenson, Rian Van Rampelbergh, Arnob Banerjee, Jenna D. Goldberg, Rachel Kobos, Amrita Krishnan, Saad Z. Usmani
Summary: Teclistamab demonstrated promising efficacy in patients with relapsed or refractory multiple myeloma, leading to high rates of deep and durable response. Common adverse events included cytokine release syndrome, cytopenias, and infections, with toxic effects mostly grade 1 or 2.
NEW ENGLAND JOURNAL OF MEDICINE
(2022)
Article
Hematology
Kristine A. Frerichs, Monique C. Minnema, Mark-David Levin, Annemiek Broijl, Gerard M. J. Bos, Marie Jose Kersten, Tuna Mutis, Christie P. M. Verkleij, Inger S. Nijhof, Patricia W. C. Maas-Bosman, Saskia K. Klein, Sonja Zweegman, Pieter Sonneveld, Niels W. C. J. van de Donk
Summary: This study evaluated the efficacy and safety of daratumumab combined with all-trans retinoic acid (ATRA) in patients with daratumumab-refractory multiple myeloma (MM). The findings suggest limited activity of the combination in reversing daratumumab resistance, possibly due to transient upregulation of CD38 expression.
Review
Oncology
Jose-angel Hernandez-Rivas, Rafael Rios-Tamayo, Cristina Encinas, Rafael Alonso, Juan-Jose Lahuerta
Summary: The increase in therapeutic alternatives for multiple myeloma patients has made the clinical scenario more complex. The choice of previously unused drugs and previous therapeutic regimens have a greater impact on treatment efficacy than the characteristics of the disease itself. New generation drugs have been developed to fight relapsed/refractory multiple myeloma.
BIOMARKER RESEARCH
(2022)
Review
Oncology
Shansa Pranami E. Jayaweera, Sacheela Prasadi Wanigasinghe Kanakanamge, Dharshika Rajalingam, Gayathri N. Silva
Summary: The proteasome plays a crucial role in regulating key regulatory proteins in cells, especially in tumor cells. Proteasome inhibitors have been proven effective in treating multiple myeloma, with carfilzomib being a second-generation inhibitor that overcomes toxicities and resistance associated with previous drugs.
FRONTIERS IN ONCOLOGY
(2021)
Article
Medicine, General & Internal
Nikhil C. Munshi, Larry D. Anderson, Nina Shah, Deepu Madduri, Jesus Berdeja, Sagar Lonial, Noopur Raje, Yi Lin, David Siegel, Albert Oriol, Philippe Moreau, Ibrahim Yakoub-Agha, Michel Delforge, Michele Cavo, Hermann Einsele, Hartmut Goldschmidt, Katja Weisel, Alessandro Rambaldi, Donna Reece, Fabio Petrocca, Monica Massaro, Jamie N. Connarn, Shari Kaiser, Payal Patel, Liping Huang, Timothy B. Campbell, Kristen Hege, Jesus San-Miguel
Summary: The phase 2 study confirmed the efficacy and safety of ide-cel in patients with relapsed and refractory myeloma, with a majority of patients achieving responses and 26% achieving MRD-negative status. Despite the high response rate, almost all patients experienced grade 3 or 4 toxic effects, including hematologic toxic effects and cytokine release syndrome.
NEW ENGLAND JOURNAL OF MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Liping Zhang, Xiaoyu Yan, Keith A. A. Fox, Stefan Willmann, Partha Nandy, Scott D. Berkowitz, Anne Hermanowski-Vosatka, Jeffrey Weitz, Alexander Solms, Stephan Schmidt, Manesh Patel, Gary Peters
JOURNAL OF THROMBOSIS AND THROMBOLYSIS
(2020)
Article
Pharmacology & Pharmacy
Ziwei Li, Jun Zhang, Yufeng Zhang, Limin Zhou, Jiajia Zhao, Yuanfeng Lyu, Long Hin Poon, Zhixiu Lin, Kenneth Kin Wah To, Xiaoyu Yan, Zhong Zuo
Summary: Altered histology, Ces1 activity, and P-gp expression in the small intestine/liver were identified as major contributing factors leading to reduced systemic exposure of simvastatin in HFHC-NASH rats, affecting absorption and hepatic elimination.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Xiaoyu Yan, Andrew Ho Wai Tse, Anna Lee, Lin Zhang, Mengbi Yang, Zhong Zuo, Gavin Matthew Joynt
Summary: The study aimed to characterize the protein binding and pharmacokinetic profile of prolonged dexmedetomidine infusion in critically ill patients. Results showed that critically ill patients had slightly lower protein binding of dexmedetomidine compared to healthy controls, but no significant explanatory pathophysiologic covariates were identified.
CLINICAL THERAPEUTICS
(2021)
Article
Pharmacology & Pharmacy
Xiaoyu Yan, Robert Bauer, Gilbert Koch, Johannes Schropp, Juan Jose Perez Ruixo, Wojciech Krzyzanski
Summary: Delay differential equations are commonly used in pharmacometric models to account for delays in pharmacokinetic and pharmacodynamic data. Nonmem 7.5 introduced several DDE solvers, with evaluations showing that EM method is more stable than FOCE for parameter estimation. These solvers provide accurate and precise solutions controlled by error tolerance parameters.
JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
(2021)
Article
Pharmacology & Pharmacy
Ly Minh Nguyen, Zhichuan Li, Xiaoyu Yan, Wojciech Krzyzanski
Summary: A quantitative systems pharmacology (QSP) model was developed to study hyporesponsiveness to rHuEPO in rats. The study found that negative feedback regulation, neocytolysis, and depletion of erythroid precursors are major factors leading to hyporesponsiveness. The model adequately characterizes time courses of rHuEPO PK and nine PD endpoints in both control and treatment groups.
JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS
(2021)
Article
Chemistry, Multidisciplinary
Hui-xi Zou, Yu-feng Zhang, Da-fang Zhong, Yong Jiang, Fei Liu, Qian-yu Zhao, Zhong Zuo, Yi-fan Zhang, Xiao-yu Yan
Summary: A population pharmacokinetic model was developed to characterize the nonstationary pharmacokinetics of furmonertinib and its active metabolite AST5902. Model-based simulation showed an increase in furmonertinib clearance during treatment, while the concentration of total active compounds appeared to be stable. Food intake, serum alkaline phosphatase, and body weight were identified as significant covariates affecting pharmacokinetics.
ACTA PHARMACOLOGICA SINICA
(2022)
Article
Chemistry, Multidisciplinary
Yufeng Zhang, Siu Kwan Wo, Wei Leng, Fang Gao, Xiaoyu Yan, Zhong Zuo
Summary: The challenge of meeting the regulatory authorities' criteria for bioequivalence (BE) in oral dosage forms, especially for products with high inter-subject variability like mesalazine enteric-coated tablet, is highlighted. This study utilizes population pharmacokinetic (PK) analysis and in-vitro in-vivo correlation (IVIVC) modeling to reveal the underlying mechanism of the high inter-subject variability. Total absorbed mesalazine is recommended for the development of the IVIVC model and BE evaluation for enteric-coated tablets.
JOURNAL OF CONTROLLED RELEASE
(2022)
Article
Pharmacology & Pharmacy
Xiaoqing Fan, Wojciech Krzyzanski, Raymond S. M. Wong, Xiaoyu Yan
Summary: This study elucidates the distinct effects of erythropoietin (EPO) and romiplostim on the fate of megakaryocyte-erythroid progenitors (MEPs), demonstrating EPO drives them toward the erythroid lineage while romiplostim stimulates megakaryopoiesis. The combination therapy of romiplostim and EPO shows promise in treating EPO-resistant anemia by enhancing erythropoiesis and inhibiting platelet production concurrently.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
Article
Pharmacology & Pharmacy
Peng Xu, Raymond S. M. Wong, Wojciech Krzyzanski, Xiaoyu Yan
Summary: The hormone erythroferrone (ERFE) may serve as a predictive factor for erythropoiesis, with its dynamics showing a correlation with the erythropoietic effects of erythropoiesis-stimulating agents (ESAs) treatment. The early increase of ERFE levels appears to be a predictor of the hemoglobin response.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Huixi Zou, Peng Xu, Raymond S. M. Wong, Xiaoyu Yan
Summary: This study demonstrates the synergistic effect of the combination therapy of recombinant human TPO and recombinant human EPO in correcting anemia, providing a quantitative basis for further optimization of the therapy.
PHARMACEUTICAL RESEARCH
(2022)
Article
Pharmacology & Pharmacy
Lin Zhang, Hongbin Sun, Yongqiang Liu, Xiaojuan Lai, Yanchun Gong, Xuefang Liu, Yong-guo Li, Yang He, Eric Y. Zhang, Xiaoyu Yan
Summary: This study developed a semi-mechanistic population pharmacokinetic model to characterize the pharmacokinetic profile of M15-2, the active metabolite of vicagrel and clopidogrel. It was found that the bioactivation of vicagrel is more efficient and less dependent on CYP2C19 than that of clopidogrel, suggesting that vicagrel may reduce the complexity of currently recommended CYP2C19-based dosage adjustment for clopidogrel.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Chemistry, Medicinal
Nan Wu, John A. Widness, Xiaoyu Yan, Peter Veng-Pedersen, Guohua An
Summary: The aim of this study was to build a mechanistic full target-mediated drug disposition (TMDD) model for rhEpo that can provide better understanding of its disposition, Epo receptor (EpoR) synthesis, and degradation in hematopoietic transplant patients with different bone marrow conditions. The model, based on a nonlinear mixed effect modeling approach, successfully characterized the pharmacokinetics (PK) of rhEpo in patients and provided insights into the dynamics of free EpoR, rhEpo-EpoR, and total EpoR. The model's predictions were supported by experimental data, and it was shown to be more robust and physiologically relevant compared to previous models.
JOURNAL OF PHARMACEUTICAL SCIENCES
(2022)
Article
Pharmacology & Pharmacy
Xiaoqing Fan, Wojciech Krzyzanski, Dongyang Liu, Raymond S. M. Wong, Xiaoyu Yan
Summary: Recombinant human erythropoietin (rHuEPO) is an effective drug for anemia treatment in patients with chronic kidney disease. However, EPO-resistance is a significant issue. Combining rHuEPO with romiplostim, a thrombopoietin receptor agonist, can overcome EPO-resistance.
Article
Pharmacology & Pharmacy
Chengcong Chen, Xiaoqing Fan, Lin Zhang, Peng Xu, Huixi Zou, Xing Zhao, Manish Gupta, Yan Summer Feng, Xu Steven Xu, Xiaoyu Yan
Summary: This study aimed to assess the feasibility of using monoclonal antibody (mAb) clearance as a biomarker for efficacy to identify potentially efficacious doses across cancer types and drug targets. The study found a clear negative association between mAb clearance and overall response rate (ORR), as well as a negative dose-clearance relationship. These findings provide important insights for guiding the development of mAbs in oncology studies.
CLINICAL PHARMACOKINETICS
(2023)
Article
Pharmacology & Pharmacy
Xueting Yao, Xiaoyu Yan, Xiaohan Wang, Ting Cai, Shun Zhang, Cheng Cui, Xiaoxu Wang, Zhe Hou, Qi Liu, Haiyan Li, Jing Lin, Zi Xiong, Dongyang Liu
Summary: The study developed a population PK model to characterize CQ PK in COVID-19 patients and found that the currently recommended dosing regimen is generally safe within the safety margin.
EUROPEAN JOURNAL OF CLINICAL PHARMACOLOGY
(2021)